tbuckley/cabot-search huggingface dataset:
Temozolomide Sensitizes <i>ARID1A</i>-Mutated Cancers to PARP Inhibitors
Authors: Zheng-Cheng Yu, Tianhe Li, Ellen Tully, Peng Huang, Chih-Ning Chen, Philipp Oberdoerffer, Stephanie Gaillard, Ie-Ming Shih, Tian-Li Wang
Journal: Cancer Research (2023)

Abstract ARID1A is a subunit of SWI/SNF chromatin remodeling complexes and is mutated in many types of human cancers, especially those derived from endometrial epithelium, including ovarian and uterine clear cell carcinoma (CCC) and endometrioid carcinoma (EMCA). Loss-of-function mutations in ARID1A alter epigenetic regulation of transcription, cell-cycle checkpoint control, and DNA damage repair. We report here that mammalian cells with ARID1A deficiency harbor accumulated DNA base lesions and increased abasic (AP) sites, products of glycosylase in the first step of base excision repair (BER). ARID1A mutations also delayed recruitment kinetics of BER long-patch repair effectors. Although ARID1A-deficient tumors were not sensitive to monotherapy with DNA-methylating temozolomide (TMZ), the combination of TMZ with PARP inhibitors (PARPi) potently elicited double-strand DNA breaks, replication stress, and replication fork instability in ARID1A-deficient cells. The TMZ and PARPi combination also significantly delayed in vivo growth of ovarian tumor xenografts carrying ARID1A mutations and induced apoptosis and replication stress in xenograft tumors. Together, these findings identified a synthetic lethal strategy to enhance the response of ARID1A-mutated cancers to PARP inhibition, which warrants further experimental exploration and clinical trial validation. Significance: The combination of temozolomide and PARP inhibitor exploits the specific DNA damage repair status of ARID1A-inactivated ovarian cancers to suppress tumor growth.
Approval of Drugs With Unmet Trial End Points
Authors: Indranil Bhattacharya, Iraj Daizadeh, Andrew S. Robertson
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abandoning the Proteinopathy Paradigm in Parkinson Disease—Not So Fast
Authors: Jeff M. Bronstein, William A. Zeiger, Chao Peng
Journal: JAMA Neurology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
MMINP: A computational framework of microbe-metabolite interactions-based metabolic profiles predictor based on the O2-PLS algorithm
Authors: Wenli Tang, Huimin Zheng, Shuangbin Xu, Pan Li, Li Zhan, Xiao Luo, Zehan Dai, Qianwen Wang, Guangchuang Yu
Journal: Gut Microbes (2023)

The gut metabolome acts as an intermediary between the gut microbiota and host, and has tremendous diagnostic and therapeutic potential. Several studies have utilized bioinformatic tools to predict metabolites based on the different aspects of the gut microbiome. Although these tools have contributed to a better understanding of the relationship between the gut microbiota and various diseases, most of them have focused on the impact of microbial genes on the metabolites and the relationship between microbial genes. In contrast, relatively little is known regarding the effect of metabolites on the microbial genes or the relationship between these metabolites. In this study, we constructed a computational framework of Microbe-Metabolite INteractions-based metabolic profiles Predictor (MMINP), based on the Two-Way Orthogonal Partial Least Squares (O2-PLS) algorithm to predict the metabolic profiles associated with gut microbiota. We demonstrated the predictive value of MMINP relative to that of similar methods. Additionally, we identified the features that would profoundly impact the prediction performance of data-driven methods (O2-PLS, MMINP, MelonnPan, and ENVIM), including the training sample size, host disease state, and the upstream data processing methods of the different technical platforms. We suggest that when using data-driven methods, similar host disease states and preprocessing methods, and a sufficient number of training samples are necessary to achieve accurate prediction.MMINP fully considers internal and mutual correlations in metabolites and microbial genes and infers metabolite information through their real joint parts.The feasibility of predicting metabolic profiles using gut microbiome data should be based on the premise of similar host disease states, similar preprocessing methods, and a sufficient number of training samples.Although the accuracy of predicted specific metabolites is affected by multiple factors, the systematic conclusions presented for predicted metabolites at higher levels (e.g., class level) are accurate, allowing metabolite prediction to be applied to the discovery of potential metabolite markers.
Diffuse Cutaneous Eruption
Authors: Katharina S. Shaw, Stephanie Sanchez-Melendez, Ruth Ann Vleugels
Journal: JAMA (2023)

A man presented with a pruritic cutaneous eruption that began on his scalp and face and over 2 months spread across most of his body. Physical examination revealed confluent salmon-colored plaques with areas of unaffected skin; waxy, exfoliative scale on the volar aspect of the hands and feet; and ectropion. He had no history of psoriasis, atopic dermatitis, or other skin disorder, and no recent viral or bacterial infection. What is the diagnosis and what would you do next?
Association of Adverse Childhood Experiences With Accelerated Epigenetic Aging in Midlife
Authors: Kyeezu Kim, Kristine Yaffe, David H. Rehkopf, Yinan Zheng, Drew R. Nannini, Amanda M. Perak, Jason M. Nagata, Greg E. Miller, Kai Zhang, Donald M. Lloyd-Jones, Brian T. Joyce, Lifang Hou
Journal: JAMA Network Open (2023)

Adverse childhood experiences (ACEs) are associated with the risk of poorer health, and identifying molecular mechanisms may lay the foundation for health promotion in people with ACEs.
Approval of Drugs With Unmet Trial End Points—In Reply
Authors: James L. Johnston, Joseph S. Ross, Reshma Ramachandran
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
SMILE: Cost-sensitive multi-task learning for nuclear segmentation and classification with imbalanced annotations
Authors: Xipeng Pan, Jijun Cheng, Feihu Hou, Rushi Lan, Cheng Lu, Lingqiao Li, Zhengyun Feng, Huadeng Wang, Changhong Liang, Zhenbing Liu, Xin Chen, Chu Han, Zaiyi Liu
Journal: Medical Image Analysis (2023)
Recent advances and prospects for lipid-based nanoparticles as drug carriers in the treatment of human retinal diseases
Authors: Shaoxue Zeng, Yingying Chen, Fanfan Zhou, Ting Zhang, Xiaohui Fan, Wojciech Chrzanowski, Mark C. Gillies, Ling Zhu
Journal: Advanced Drug Delivery Reviews (2023)

The delivery of cures for retinal diseases remains problematic. There are four main challenges: passing through multiple barriers of the eye, the delivery to particular retinal cell types, the capability to carry different forms of therapeutic cargo and long-term therapeutic efficacy. Lipid-based nanoparticles (LBNPs) are potent to overcome these challenges due to their unique merits: amphiphilic nanoarchitectures to pass biological barriers, vary modifications with specific affinity to target cell types, flexible capacity for large and mixed types of cargos and slow-release formulations for long-term treatment. We have reviewed the latest research on the applications of LBNPs for treating retinal diseases and categorized them by different payloads. Furthermore, we identified technical barriers and discussed possible future development for LBNPs to expand the therapeutic potential in treating retinal diseases.
Total stricture of liver transplant biliary anastomosis resolved with peroral digital cholangioscopy and the non-flexible end of a 0.018-inch biliary guidewire
Authors: Maria Puigcerver-Mas, Albert Garcia-Sumalla, Josefina Lopez-Dominguez, Laura Llado Garriga, Joan B. Gornals
Journal: Endoscopy (2023)

A 64-year-old man underwent orthotopic liver transplantation due to hepatocellular carcinoma on liver cirrhosis diagnosed 2 years earlier. Three months after transplantation surgery, he presented with jaundice, and a cholangio magnetic resonance imaging scan revealed a biliary anastomosis stricture with marked kinking and retrograde dilatation. A multidisciplinary committee decided on an endoscopic approach.
Primary malignant melanoma of the pancreas diagnosed by endoscopic ultrasonography-guided fine-needle biopsy
Authors: Shenglin Xu, Yaping Ye, Wen Guo, Side Liu, Yue Li
Journal: Endoscopy (2023)

Endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) plays an important role in obtaining pathology specimens from pancreatic lesions. FNB needles have been designed to acquire larger "core" specimens that preserve tissue architecture and permit histologic evaluation and immunohistologic staining [1] [2]. In this study, we report an extremely rare case of primary pancreatic melanoma diagnosed by EUS-FNB using a 22-gauge Franseen needle.
The climate crisis and violence against children
Authors: Jorge Cuartas, Amiya Bhatia, Daniel Carter, Lucie Cluver, Carolina Coll, Catherine E Draper, Elizabeth Donger, Frances Gardner, Hernando Grueso, Bess Herbert, Jamie Lachman, Najat Maalla M'jid, Frederique Seidel, Orla Kelly
Journal: The Lancet Child & Adolescent Health (2023)
Moderators of the effect of therapeutic exercise for knee and hip osteoarthritis: a systematic review and individual participant data meta-analysis
Authors: Melanie A Holden, Miriam Hattle, Jos Runhaar, Richard D Riley, Emma L Healey, Jonathan Quicke, Danielle A van der Windt, Krysia Dziedzic, Marienke van Middelkoop, Danielle Burke, Nadia Corp, Amardeep Legha, Sita Bierma-Zeinstra, Nadine E Foster, Jenny Brown, Carol Ingram, Sheila Hickson, Robert Taylor, Christine Walker, J Haxby Abbott, Kelli Allen, Kim Bennell, Daniel Bossen, Kanda Chaipinyo, Tom Cochrane, Mariëtte de Rooij, May Arna Risberg, G Kelley Fitzgerald, Helen French, Leigh Hale, Marius Henriksen, Rana S Hinman, Marijke Hopman-Rock, Michael Hurley, Justin Keogh, Cindy Veenhof, Jesper Knoop, Inga Krauss, Pazit Levinger, Christopher McCarthy, Stephen P Messier, Ari Heinonen, Havard Osteras, Shahnawaz Anwer, Ana Cristina R Lacerda, Shankar Ganesh, Benjamin Steinhilber, Yusuke Suzuki, Michael A Hunt, Laura Talbot, Carolien Teirlinck, Michael Doherty, Pao-Feng Tsai, Jason A Wallis, Merve Yilmaz Menek
Journal: The Lancet Rheumatology (2023)

Many international clinical guidelines recommend therapeutic exercise as a core treatment for knee and hip osteoarthritis. We aimed to identify individual patient-level moderators of the effect of therapeutic exercise for reducing pain and improving physical function in people with knee osteoarthritis, hip osteoarthritis, or both.
Rapid reduction in Staphylococcus aureus in atopic dermatitis subjects following dupilumab treatment
Authors: Eric L. Simpson, Patrick M. Schlievert, Takeshi Yoshida, Stephanie Lussier, Mark Boguniewicz, Tissa Hata, Zelma Fuxench, Anna De Benedetto, Peck Y. Ong, Justin Ko, Agustin Calatroni, Amanda K. Rudman Spergel, Marshall Plaut, Sally A. Quataert, Samuel H. Kilgore, Liam Peterson, Ann L. Gill, Gloria David, Tim Mosmann, Steven R. Gill, Donald Y.M. Leung, Lisa A. Beck
Journal: Journal of Allergy and Clinical Immunology (2023)

Atopic dermatitis (AD) is an inflammatory disorder characterized by dominant type 2 inflammation leading to chronic pruritic skin lesions, allergic comorbidities, and Staphylococcus aureus skin colonization and infections. S aureus is thought to play a role in AD severity.
The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure
Authors: Ruben Hernaez, Constantine J. Karvellas, Yan Liu, Sophie-Caroline Sacleux, Saro Khemichian, Lance L. Stein, Kirti Shetty, Christina C. Lindenmeyer, Justin R. Boike, Douglas A. Simonetto, Robert S. Rahimi, Prasun K. Jalal, Manhal Izzy, Michael S. Kriss, Gene Y. Im, Ming V. Lin, Janice H. Jou, Brett E. Fortune, George Cholankeril, Alexander Kuo, Nadim Mahmud, Fasiha Kanwal, Faouzi Saliba, Vinay Sundaram, Thierry Artzner, Rajiv Jalan, Atef Al Attar, Kambiz Kosari, Richard Garcia, Gevork Salmastyan, William Cranford, Preet Patel, Pei Xue, Soumya Mishra, Madison Parks, Gianina Flocco, Jing Gao, Tiffany Wu, Priya Thanneeru, Vikrant Reddy, Jing Gao, Mariana Hurtado, Islam Mohamed, Ross Vyhmeister, Christine R. Lopez, Braidie Campbell, Adam C. Winters, Mary Ann Simpson, Xiaohan Ying
Journal: Journal of Hepatology (2023)
IL-4 receptor alpha blockade dampens allergic inflammation and upregulates IL-17A expression to promote S aureus clearance in antigen sensitized mouse skin
Authors: Juan-Manuel Leyva-Castillo, Alex McGurk, Maria Strakosha, Daniela Vega-Mendoza, Sophia E.M. Smith, Kelsey Stafstrom, Megan Elkins, Janet Chou, Yui-Hsi Wang, Raif S. Geha
Journal: Journal of Allergy and Clinical Immunology (2023)
Disease stratification in GCA and PMR: state of the art and future perspectives
Authors: Alessandro Tomelleri, Kornelis S. M. van der Geest, Muhammad Asim Khurshid, Alwin Sebastian, Fiona Coath, Daniel Robbins, Barbara Pierscionek, Christian Dejaco, Eric Matteson, Yannick van Sleen, Bhaskar Dasgupta
Journal: Nature Reviews Rheumatology (2023)
Sources and Sinks of Serine in Nutrition, Health, and Disease
Authors: Michal K. Handzlik, Christian M. Metallo
Journal: Annual Review of Nutrition (2023)

Amino acid dysregulation has emerged as an important driver of disease progression in various contexts. l-Serine lies at a central node of metabolism, linking carbohydrate metabolism, transamination, glycine, and folate-mediated one-carbon metabolism to protein synthesis and various downstream bioenergetic and biosynthetic pathways. l-Serine is produced locally in the brain but is sourced predominantly from glycine and one-carbon metabolism in peripheral tissues via liver and kidney metabolism. Compromised regulation or activity of l-serine synthesis and disposal occurs in the context of genetic diseases as well as chronic disease states, leading to low circulating l-serine levels and pathogenesis in the nervous system, retina, heart, and aging muscle. Dietary interventions in preclinical models modulate sensory neuropathy, retinopathy, tumor growth, and muscle regeneration. A serine tolerance test may provide a quantitative readout of l-serine homeostasis that identifies patients who may be susceptible to neuropathy or responsive to therapy.
Rescue of hearing by adenine base editing in a humanized mouse model of Usher syndrome type 1F
Authors: Cole W. Peters, Killian S. Hanlon, Maryna V. Ivanchenko, Eric Zinn, Elizabeth F. Linarte, Yaqiao Li, Jonathan M. Levy, David R. Liu, Benjamin P. Kleinstiver, Artur A. Indzhykulian, David P. Corey
Journal: Molecular Therapy (2023)
Dyslipidemia
Authors: Marios Arvanitis, Charles J. Lowenstein
Journal: Annals of Internal Medicine (2023)

Dyslipidemia is an important risk factor for coronary artery disease and stroke. All persons with dyslipidemia should be advised to focus on lifestyle interventions, including regular aerobic exercise, a healthy diet, maintenance of a healthy weight, and abstinence from smoking. In addition to lifestyle interventions, lipid-lowering therapy should be considered for persons at moderate to high risk for atherosclerotic cardiovascular disease based on validated risk equations. Statin therapy is the first-line medical treatment for dyslipidemia due to its effectiveness and favorable adverse effect profile, but newer treatments provide additional tools for clinicians to effectively treat dyslipidemia.
TRLS-02. FEASIBILITY OF EVALUATING ABEMACICLIB NEUROPHARMACOKINETICS OF DIFFUSE MIDLINE GLIOMA USING INTRATUMORAL MICRODIALYSIS
Authors: Sadhana Jackson, John Glod, Cody Peer, William Figg, Mahalia Dalmage, Desmond Brown
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates &amp;lt;10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment response. METHODS This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18-39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are &amp;gt;10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression. DISCUSSION The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05413304. Registered June 10, 2022, Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis; https://clinicaltrials.gov/ct2/show/NCT05413304?term=22c0003&amp;draw=2&amp;rank=1
DIPG-47. DISCOVERING A MOLECULAR BASIS FOR VULNERABILITY OF H3K27M-DMG TO HISTONE DEACETYLASE INHIBITORS
Authors: Danyelle Paine, Yue Hao, Nanyun Tang, Matt Biery, Nicholas Vitanza, Michael Berens
Journal: Neuro-Oncology (2023)

Abstract Using two H3K27M-DMG treatment-naive preclinical models (PBT22 and PBT29), we detected a 20-fold differential response to the histone deacetylase inhibitor, Quisinostat. PBT-22 harbors mutations in H3F3A, TP53, and ASXL2, while PBT-29 has mutations in H3F3A, TP53, PIK3CA and FGFR1. Acetylation and deacetylation of wtH3 alter chromatin structure as part of normal regulation of gene expression. The methionine substitution for Lysine in H3K27M removes this histone from participating in acetylation/deacetylation regulated gene expression. Concomitantly, H3K27M induces a marked reduction in global acetylation of histone tails on wtH3. In the native state of H3K27M DMG with hypoacetylated H3, we posit that the specific pattern of nucleosome integration with genes responsible for cell survival/death underlies the differential vulnerability of DMGs to HDACi. Additionally, the nucleosome integration pattern with cell survival/death genes may be based on the relative abundance of wtH3wt versus H3K27M- histones. Following Quis treatment (48 hrs) in both preclinical models, total wtH3ac protein abundance increased 3-fold, suggesting HDACi stabilizes or impedes K27 acetylated H3 histone turnover. Comparison of differentially expressed genes (DEGs) from control and Quis-treated PBT22 and PBT29 will seed gene ontology analysis focusing on chromatin remodeling, cell death, and growth arrest pathways accounting for differential vulnerability. Findings will be validated by measuring transcripts and proteins (qRT-PCR and ELISA or mass spectrometry) from analytes from a larger panel of DMG cell lines. The data depicts DMG preclinical models with large differential sensitivity to Quis. The long-term goal is to discover a molecular profile of DMGs predictive of the vulnerability to HDACi. The discovery exercise is also likely to yield insight into the development of resistance to HDAC inhibitors.